The UK experience of the process of legalization of "mitochondrial replacement techniques" has been an object lesson in how a well-oiled technocratic machine can manipulate public opinion in order to achieve the desired result or simply ignore negative public responses.

In the UK, reproductive technologies are regulated by the Human Fertilisation and Embryology Act, which was last updated in 2008. The Act prohibits the implantation in a woman of embryos produced by any means other than fertilization of an egg by a sperm. However, because the possibility of 'mitochondrial replacement' was envisaged at that time, there is a provision which allows the Secretary of State to make regulations permitting the use of such embryos, on a case-by-case basis. We are now at this stage, and it is expected that the government will publish the regulations this autumn. It is important to understand that there will be no significant parliamentary debate on the regulations or any possibility of amending them: the procedure simply involves a one hour discussion by a committee which can only approve or reject regulations. In essence, this is a rubber-stamping procedure.

Unlike nearly every other European country, the UK has not signed the Council of Europe Convention on biomedicine and human rights, which prohibits any intentional changes to the human germ line.

How to get the answer that you want

The process of legalization of 'mitochondrial replacement techniques' began in the spring of 2012 with a report by the Nuffield Council on Bioethics, an independent academic body funded by the Nuffield Foundation.

As expected, the Council approved the use of these techniques. Its main innovation was to decide that the techniques constituted a form of manipulation of the human germ line, something that elite opinion had previously denied. In recognizing that this crucial ethical line was being crossed, the Council insisted that any attempt to manipulate nuclear DNA through genetic modification would require further ethical consideration.

Following the Nuffield Council report, the HFEA announced its main public consultation on the ethical aspects in mid-2012. U.S. readers will probably look upon the UK regulatory system, and the existence of the HFEA, as a good thing, at least in comparison to the lack of statutory regulation in the U.S. The existence of the HFEA plays a crucial role in reassuring the public that these difficult ethical issues are being responsibly considered by the powers that be. But in reality, although the HFEA is obliged to maintain some degree of separation between itself and the IVF industry and entrepreneurial scientists that it regulates, in terms of its ideological position, the HFEA is in complete concord with those industries. In fact, its current head of policy was formerly director of the Progress Educational Trust, a body set up in the 1980s that has always argued for liberalization and acceptance of every new technology.

The HFEA has become practiced in using public 'consultation' to advance the use of such technologies and to weaken ethical restraints upon them. In general, the HFEA is well ahead of public opinion, but only on one occasion has it failed to carry the public with it. That was in 2003, when it issued a consultation arguing for the legalization of sex selection for social reasons. An extremely strong negative public response forced HFEA to abandon that position.

HFEA's consultation documents are written with a technocratic bias that makes little effort towards even-handedness. In recent years it has become increasingly overconfident. For example, in 2009 the new chair of the HFEA, Lisa Jardine, announced in a newspaper interview that she was in favor of paying egg donors for their services in advance of the HFEA's consultation. In this case it has simply ignored the results of the consultation.

The HFEA's manipulation of the consultation process had two main elements: (i) misleading scientific information, and (ii) biased ethical discussion.

Bad science

The key piece of scientific misinformation that was crucial to the ethical misunderstanding of these techniques was the statement, endorsed by major scientific institutions, that mitochondria act as mere "batteries" for cells, and that mutations in mitochondrial genes have no effect on an individual's identity. The statement made an analogy with a laptop computer; its batteries do not affect the programs or data on the laptop. The purpose of this endlessly-repeated statement was to minimize the ethical significance of the changes to the germ line involved. (In these discussions, 'identity' was never clearly defined, but the general impression given was that it referred to visible physical differences, and perhaps personality.)

This piece of scientific nonsense is a classic example of the reductionist models of biology which dominate public debate and are clearly used by advocates of new technologies to manipulate the debate. Living organisms are simply not like computers: they are complex, whereas computers are merely complicated. Even were it true that the functions of mitochondria are restricted to generating ATP, the idea that energy metabolism can somehow be isolated from the rest of the physiology of the organism is biologically laughable. This is the same mentality that leads synthetic biologists to claim that they can separate and redesign different 'modules' of cellular function. One might imagine that such ambitious scientific claims would be backed up by detailed scientific evidence, but insofar as it is possible to determine the origin of what has now become an urban myth, the claim is entirely unsupported. The main quoted 'scientific' reference for the claim is a submission by those two august medical authorities, the UK Medical Research Council and the Wellcome Trust, to the Nuffield Council enquiry, which contains no scientific references whatever for this claim.

In reality, energy metabolism is entangled with many other aspects of cellular function, and mitochondria have a number of other roles. Mitochondria are emerging as a central element in the overall regulation of cell function; for example, it is becoming clear that there is constant epigenetic modification of nuclear DNA according to mitochondrial states, including the level of production of oxygen free radicals. Thus, it is not surprising that they are implicated in a variety of disease states. The New Scientist magazine recently summarized a number of examples of mitochondrial function affecting things other than ATP levels.[1] Thus, the idea that mitochondria do not affect aspects of a person's physiology that contribute to their identity is bound to be wrong, although our knowledge of these complexities is still rudimentary. A similar claim might be made about the majority of genes in the nuclear genome that have 'housekeeping' functions. But the attempt to suggest that mitochondrial function is cleanly separable from other aspects of cell function in the same way that mitochondrial DNA is in a different compartment from nuclear DNA shows how DNA-centered reductionist biology serves the effort to convince the public that they did not need to worry about this form of genetic manipulation.

In examining the way in which scientifically misleading information by key scientific authorities has been used to manipulate the public debate, one is irresistibly reminded of the example of human-animal hybrid embryos. In 2007 and 2008, while the HFEA Act was being updated, the UK witnessed a massive campaign by scientists (including several UK Nobel Prize winners) to legalize the creation of human-animal hybrid embryos which, we were told, were vital to medical research. Despite warnings by the author that such embryos were worthless for scientific research, the UK Parliament duly legalized their use. But in the following year, the Medical Research Council was forced to reject funding applications from the same research center that is spearheading the push for mitochondrial replacement because they lacked scientific merit.

In addition to misleading scientific statements for general public consumption, the HFEA has also conducted scientific reviews of the safety of mitochondrial replacement. There are many problems with the review panel's treatment of these issues, all of which tend in the same direction, towards permitting clinical trials as soon as possible. The panel has consistently adopted a standard of proof that is neither precautionary nor 'evidence-based,' but in fact anti-precautionary: 'There is no evidence to suggest that the techniques are unsafe.' There are certainly plenty of reasons for thinking that the techniques might be unsafe and one would have thought that under legislation that makes the welfare of the child the paramount consideration, a precautionary approach would be used.

The most obvious safety concern about these techniques is the possibility that the extremely invasive manipulation of embryos may damage the embryos, for example by creating epigenetic problems which may affect the child's health. It is well known that assisted reproductive technologies can create epigenetic errors, even when the manipulations are relatively minor, as in basic IVF. In general, the more invasive the manipulation, the greater risk of epigenetic problems; the techniques under consideration would involve the most invasive manipulations in clinical use to date. The few published papers on the mitochondrial replacement techniques clearly show that the manipulations damage the embryos, so that a relatively low percentage survive to the blastocyst stage. Given this, it is reasonable to expect that the surviving embryos will have more subtle damage, and it is imperative that comprehensive safety studies focusing on possible epigenetic issues in these embryos are concluded before clinical trials are permitted. However, the HFEA panel merely recommends such studies rather than requiring them. The downplaying of these issues is consistent with the DNA-centered reductionist biology which has already been noted: The regulators, like the lay public, are assuming that creating a healthy embryo is simply a matter of making sure it has the right DNA.

Bad ethics

The HFEA's misrepresentation of ethical issues are too numerous to detail here; Human Genetics Alert has prepared an in-depth analysis of these which is available on request. In all its materials, where HFEA presented critiques, it either under- or over-states the argument, and in every instance the discussion is presented in the form: "critics claim that ... but others argue that... ." Its treatment of the crucial issue of germ line manipulation (see article in this issue by Cussins and Darnovsky) is entirely inadequate. And it entirely fails to present a conventional risk/benefit analysis and repeatedly suggests that the techniques are the only way in which mothers who carry these conditions can have healthy children. Although the existence of conventional egg donation as an alternative is very briefly mentioned, it nowhere acknowledges that this means that the sole benefit of the new techniques is that the mother can be the nuclear genetic parent of her child, and that this is not a medical benefit to either mother or child, but merely a social benefit. In our view, given the safety risks of the techniques, this social benefit cannot justify exposing a child to the potentially harmful health consequences of the techniques. In my view, it is difficult to understand the devotion of millions of pounds of research funding to the development of techniques which will deliver such a benefit to a very small group of people. To cross the crucial ethical line of non-manipulation of the human genome for such a benefit is simply absurd.

Despite the HFEA's bias in favor of legalization of the techniques, a strong majority of responses to the online consultation opposed legalization. However, the HFEA preferred to take notice of the results of its focus groups and opinion poll, both of which involved uninformed participants whose opinions are easier to manipulate. Recent opinion polls have contradicted the HFEA's opinion poll results and suggested that less than 20% of the population actually supports the techniques. Its press statements glossed over the negative response to the online consultation and simply declared 'broad public support' for the techniques. The UK Department of Health has done the same thing in its consultation on proposed regulations.

Conclusion

The experience of this public consultation process has been depressing for those who would support democratic control of reproductive technologies. The supporters of the techniques created an extremely well coordinated campaign, exploiting the public's natural sympathy for families with sick children. The 'watchdog' body acted more like a cheerleader for the campaign, consistently manipulating both scientific fact and ethical issues in order to achieve the desired results, and when the public response was negative, simply ignoring that fact. A compliant media failed to raise the critical issues. It can hardly be claimed that Britain has undergone the public debate necessary to take a decision of this historical magnitude.

It is difficult to say whether an unregulated 'Wild West' or a technocratic regulator willing to manipulate facts to achieve its preferred result is the least desirable environment for responsible use of reproductive technologies. A better third alternative must await the advent of a genuine citizens' movement on these issues.

David King, PhD, is a former molecular biologist and is Director of Human Genetics Alert (www.hgalert.org).